Dissecting mechanisms of mRNA translational control by specialised ribosomes

The average cell contains ~10 million ribosomes, comprised of ~80 ribosomal proteins and 4 rRNAs. Until recently it was thought that all ribosomes were the same. But substantial new evidence has revealed that ribosome heterogeneity provides an additional level of translational control. These different ribosome populations are termed 'specialised ribosomes'. How these specialised ribosomes translate specific mRNA pools remains a mystery. This project aims to understand how changes in ribosome composition enable translation of specific mRNA pools by altered ribosome structures.

We have discovered differences in ribosome composition in Drosophila melanogaster brain and testis (project currently funded by a BBSRC grant). mRNA translation is particularly important during sperm production and neural function so it will be exciting to understand how this novel mechanism of gene regulation is achieved.

Using a cutting-edge combination of translatomics and structural biology this project will uncover the function and mechanism of specialised ribosomes. We will determine which mRNAs specialised ribosomes translate using Ribo-Seq (Next Generation Sequencing) and how specialisation is achieved using cryo-EM. These approaches are data intensive and represent priority bioscience skills areas, as both involve large data sets and bioinformatic analysis. This work has potential to shed light on the underlying mechanism of human diseases caused by mutations to ribosomal proteins e.g. Diamond-Blackfan.